Nationwide, homeless populations are at risk for HIV infection due to disproportionate use of injection drugs, unprotected sexual activity, prostitution and victimization. Infection with the Hepatitis B Virus (HBV) and the Hepatitis C Virus (HCV) is high among homeless adults as they share risk factors with HIV. Hepatitis A Virus (HAV) is also high among populations vulnerable to HBV, HCV, and HIV as modes of transmission for HAV overlap with those of HBV, HCV, and HIV. Thus, education and screening programs for HAV, HBV, HCV, and HW, combined with vaccination programs for HAV and HBV, can significantly decrease Hepatitis-related morbidity and mortality. However, homeless persons, many of whom may be contending with drug and alcohol abuse and unemployment, and live in a disorganized world with little access to health and social services, are often non-compliant. In this prospective two group quasi-experimental design, we will evaluate with approximately 1000 sheltered men and women in the Skid Row area of Los Angeles, the effectiveness of a theoretically-based HAV/HBV vaccination intervention focused primarily on completion of the combined Twinrix HAV/HBV vaccination series and secondarily on risk reduction of HAV, HBV, HCV, and HIV. We will also collect data on the relative cost of each of these programs in terms of completion of HAV/HBV vaccination, the cost effectiveness of improving vaccination completion, the cost per sero-protected case, and the cost per infection prevented. Once determined eligible, participants will be randomized by shelter into one of two programs: a Nurse Case Managed Plus Incentive and Tracking (NCMIT) program and a Standard Plus Incentive and Tracking (SIT) program. The proposed study is innovative in that the comparison of the SIT and NCMIT programs will allow us to look at the effect of a standard intervention combining brief education, incentives and tracking with that of a similar intervention that also includes nurse case management on completion of the HAV/HBV vaccination. Participants in the two programs will receive the 3-series vaccination by trained research nurses at the study clinic over six months, along with either the NCMIT, or the SIT program. All participants will be assessed at baseline and six- and twelve-month follow-up using a battery of psychosocial, behavioral, health and physical status, as well as HAV, HBV, HCV, and HIV sero-status measurements. This proposed study supports the National Drug Abuse Research Initiative as it is focused on assessing the effectiveness of intervention programs promoting the prevention of medical consequences of HAB, HBV, HCV, and HIV in homeless and drug abusing populations.